Molecular Biology of Oral Alkali Production

口服碱生产的分子生物学

• 批准号: 6765103
• 负责人: Robert A Burne
• 金额: $ 25.21万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6765103
• 关键词: Streptococcus; acid base balance; acidity /alkalinity; aminohydrolases; ammonia; arginine; bacterial genetics; carbohydrates; dental caries; disease /disorder model; enzyme activity; enzyme induction /repression; enzyme mechanism; genetic regulation; genetic regulatory element; laboratory rat; microorganism metabolism; molecular biology; molecular cloning; mutant; oral bacteria; oral health; pathologic process; transcription factor; urea; urease

DESCRIPTION (provided by applicant): Alkali generation, in the form of ammonia, is a major impediment to the initiation and progression of dental caries. There is also indirect evidence to support that ammonia production impacts calculus deposition by promoting mineral precipitation, and it may also exacerbate periodontal diseases by impairing the function of normal host immune and repair processes. There are two major sources of ammonia in the mouth: urea and arginine, which are hydrolyzed by ureases and the arginine deiminase system (ADS) of oral bacteria, respectively. During the previous funding periods, substantial insight was gained about the molecular architecture, genetic regulation, the role of ureases of oral bacteria in physiologic homeostasis and the importance of alkali generation in caries inhibition. This proposal builds on our previous studies with the ureases of oral bacteria, focusing on two fundamental areas directly related to the molecular biology, physiology and role in oral diseases of ammonia production. The first continues the studies we have developed during the previous funding periods on the molecular biology of urea catabolism by oral microorganisms and the second goal is to thoroughly characterize the arginine deiminase systems (ADS) of two oral streptococci. To accomplish our goals, we have organized the project under two specific aims: Aim 1. Continued analysis of the genetics, physiology and role in oral ecology and disease of bacterial ureases focusing primarily i) on the pH- and carbohydrate-dependent expression of the urease of Streptococcus salivarius, but also ii) on the utility of recombinant, urease-producing bacteria in inhibition of dental caries and iii) on factors that may affect the ability of oral microorganisms to carry out ureolysis in the human oral cavity. Aim 2. Molecular analysis of the arginine deiminase system of Streptococcus gordinii and Streptococcus rattus focusing i) on the cis- and trans-acting factors governing induction by arginine, and repression by glucose or oxygen, ii) analysis of the role of the ADS in inhibition of the initiation and progression of dental caries using of ADS-deficient mutants of S. gordonii and S. rattus, or recombinant, arginolytic S. mutans, and iii) physiological analysis of arginine transport and analysis of the effects of fluoride on alkali-generation via the ADS. This research will provide insights into new ways to control caries and other oral infectious diseases by manipulating the capacity or oral microorganisms to produce ammonia and to modulate the pH of oral biofilms.

描述（申请人提供）：碱产生，以氨的形式， 是龋齿的启动和进展的主要障碍。那里 也是间接证据以支持氨产生积极 通过促进矿物沉淀来沉积，并且也可能加剧 牙周疾病通过损害正常宿主免疫和修复的功能 过程。口腔中有两个主要来源：尿素和 精氨酸，由尿素和精氨酸脱节酶系统水解 口服细菌的（广告）。在前面的资金期间， 关于分子结构，遗传的实质性见解 调节，口服细菌在生理稳态和 碱产生在龋齿抑制中的重要性。该建议建立 关于我们先前对口服细菌尿素的研究，重点是 与分子生物学，生理学和 在氨产生口腔疾病中的作用。第一个继续我们的研究 在前前的资金期间已经开发了有关分子生物学的 口服微生物的尿素分解代谢，第二个目标是彻底 表征两个口服链球菌的精氨酸脱节酶系统（ADS）。到 实现我们的目标，我们以两个具体目标组织了该项目： 目标1。对口腔生态学中遗传学，生理学和作用的持续分析 和细菌尿素的疾病主要是i） 链球菌唾液的尿素酶的碳水化合物依赖性表达， 但也ii）关于重组，产生脲酶的细菌的实用性 抑制龋齿和iii）可能会影响可能影响能力的因素 口服微生物在人口腔中进行尿液溶解。 目的2。链球菌精氨酸脱节酶系统的分子分析 gordinii和链球菌的聚焦i） 精氨酸诱导的因素，葡萄糖或氧气抑制， ii）分析广告在抑制启动和 使用AD缺乏链球菌的龋齿进展 S. rattus或重组，精氨酸葡萄干和III）生理 精氨酸转运和氟化物对影响的分析 通过广告的碱产生。这项研究将提供有关新的见解 通过操纵龋齿和其他口腔传染病来控制龋齿和其他口腔传染病 能力或口服微生物产生氨和调节pH的pH 口服生物膜。